Human monocytes synthesize and release IL-1 in the form of either IL-la or IL-18 upon stimulation with a variety of soluble agents such as TPA (a known activator of protein kinase C (PKC), Concanavalin-A (Con-A), and Lipopolysaccharide (LPS) . Initial studies focused on the production and release of IL-15. These stimuli varied in the ability to stimulate production and release of IL-1beta. With respect to total IL-1beta production, TPA proved to be a weak stimulus while Con-A was a strong stimulus of approximately equal potency to LPS. LPS consistently stimulated release of IL-1beta, while TPA and especially Con-A were weak and inconsistent stimulators of release. With respect to LPS, release of IL-13 appeared to occur at a dose of activator associated with maximum response for IL-1beta production. EC50 concentrations stimulated production of IL-113, but no release was apparent. Similar principles applied for Con-A, although it proved to be a weak and inconsistent stimulator of release when compared to LPS. Some difference was found between LPS and Con-A-stimulated release of IL-1beta with respect to time. LPS stimulated release of IL-13 within 3 hours of activation, and release continued to increase up to 12 hours. With Con-A, production of IL-1beta occurred as early as 3 hours, but no release was seen for up to 12 hours after activation. Con-A and LPS stimulated the production of 5 to 10-fold less IL-1alpha than IL-1beta.